Bordetella bronchiseptica has been established as the principal cause of the widespread disease in swine commonly referred to as "turbinate atrophy", because, following the primary infection, the nasal turbinate bones frequently undergo serious deterioration. See Canad. J. Comp. Med., 31, 53-57 (1967), and literature references cited therein. Bordetella bronchiseptica bacteria can persist in the nasal cavities, leading to infection of the susceptible offspring of breeding sows.
Baby pigs become infected with B. bronchiseptica early in life (under 4 weeks of age) which makes the problem of effective protection particularly difficult, since the immunity system of very young pigs does not respond satisfactorily to vaccines. For effective antibody production, vaccines are usually administered to pigs at an age of about 6 to 8 weeks. By that age, however, if the pigs have become infected with B. bronchiseptica damage to the turbinate bones may well occur, even though the pigs become immunized to the infection.
The first treatment proven to be of value in reducing the incidence of infection of young pigs was the administration of a sulfonamide therapeutic agent, such as sulfamethazine or sulfaethoxypyridazine, in the rations fed to the breeding herds. This method was reported in the literature and patented by Dr. William P. Switzer: Vet. Med., 58, 571-575 (1963); and U.S. Pat. No. 3,336,190. However, the effectiveness of sulfonamide therapy in eliminating Bordetella bronchiseptica infection has been limited by development of sulfonamide-resistant strains of the organism. For example, a study in 1967 found that isolates of B. bronchiseptica recovered from 80% of the herds inspected were resistant to sulfonamide. Am. J. Vet. Res., 30, 1621-1624 (Sept., 1969). This data emphasized the recognized need for additional drugs, or, in particular, effective immunizing agents. Prior to the present invention, however, no other preventative treatment suitable for use in the commercial raising of swine has been developed.
It was found that the introduction of live cells of a low-virulence strain of B. bronchiseptica into the nasal cavities of non-immune swine would cause a relatively mild infection, and that thereafter the swine would be immune to further infection, including infection by more virulent strains of the organism. See J. Vet. Res., 30, 1161-1166 (July, 1969). One such low virulent strain, which was not publicly available, was identified by the private code designation of "Strain D-1". This is the same strain used for preparing the killed whole cell parenteral vaccine of the present invention. However, in prior work, live cells of the Strain D-1 were found to persist in the nasal cavities of recovered swine. Therefore Strain D-1 was ruled out as a live whole cell intranasal vaccine. Moreover, no other strain of B. bronchiseptica was known which would produce immunity, and thereafter be self-clearing from the nasal passages of the immunized swine.
Attempts were also made to develop a vaccine from killed cells of B. bronchiseptica which would induce immunity by parenteral administration. One of the first such experimental vaccines was prepared from a virulent strain of B. bronchiseptica (identified as "Strain B"). But this whole cell-vaccine failed to induce resistance to nasal infection as reported by Harris, D. L., and Switzer, W. P.: Am. J. Vet. Res., 30, 1161-1166 (July, 1969). Because of the failure of such whole-cell parenteral vaccines, Harris and Switzer postulated that "exposure of the pig to the internal antigens of B. bronchiseptica may be necessary for the production of resistance against nasal infection." Am. J. Vet. Res., 33, 1972, at 1981-1982 (Oct., 1972). This theory proved incorrect. Vaccines prepared from disrupted cells (sonicated) of B. bronchiseptica, Strain D-1, failed to prevent B. bronchiseptica infection, but induced an accelerated clearance by 40 days post challenge (A.J. Vet. Res., 33, 1972, at 1979 and 1981). It was concluded that the type of resistance induced by a parenteral vaccine containing the liberated antigens of killed cells was different than the immunity of swine which had recovered from intranasal infection with live B. bronchiseptica. The goal of effective immunization against the infection remained to be achieved, and no answer to this baffling problem was apparent.
The state of art was summarized by D. O. Farrington and W. P. Switzer in a paper entitled "Resistance to Bordetella Rhinitis," Proceedings the George A. Young Conference on Advances in Swine Repopulation and the Thirteenth Annual Nebraska SPF Conference, Lincoln, Nebraska, July 23-24, 1973, pp. 44-52. It was reported that parenteral immunization of swine with B. bronchiseptica bacterins is known to accelerate nasal clearance of B. bronchiseptica infections, and that development of the gross lesions associated with atrophic rhinitis appears to be significantly inhibited in suitably immunized swine. Trials with experimental B. bronchiseptica bacterins as summarized in Table 1 show positive results. However, it was concluded: "Many unanswered questions remain before the development of a practical immunizing agent against Bordetella rhinitis becomes a reality."